Recent reports have implicated vinyl chloride (VC) as the causative agent of angiosarcoma of the liver amongst workers in the manufacture of polyvinyl chloride (PVC) from VC; PVC is widely used in various plastic products. Commercial PVC and products made from it contain approximately 2 - 7% free VC and hence VC may be a widely distributed environmental carcinogen. Exposure of rats to VC by inhalation has shown that it causes the same type of liver tumors as those observed in humans; thus experiments in rats constitute an ideal model for determination of the mechanism of action of VC and for studies on the carcinogenicity of compounds related to VC. Based on our previous studies, it is likely that the activated carcinogenic intermediate is chloroethylene oxide or chloroacetaldehyde. Our objective is to determine the nature, site of formation and mode of action of the activated carcinogenic intermediate. Studies on the metabolism of VC will be conducted on rat liver homogenates and intracellular fractions and components derived from it, in vitro and in vivo. Similar in vitro studies on the metabolism of VC and of trichloroethylene will be carried out on human liver obtained from fresh autopsy material. The malignant transformation of primary rat embryo cells in vitro by VC, VC epoxide and chloroacetaldehyde will be determined by procedures shown earlier to be successful for the induction of sarcomas in rats by diepoxybutane. The carcinogenic activity of VC, VC epoxide, and chloroacetadehye to rats will be determined. Similar studies will be carried out on a closely related analog of VC, trichloroethylene. These studies will lead to new insights concerning occupational and environmental carcinogens and their mechanism of action in animals and man.